a study of rm-718 in healthy subjects and in patients with ho

Conditions: Hypothalamic Obesity

Summary: the purpose of this study is to evaluate the safety, tolerability, and pk of rm-718 in healthy subjects with obesity and in patients with hypothalamic obesity (ho).

this is a first-in-human and first-in-patient, 3-part study that includes the evaluation of safety, tolerability, and pk of: single ascending doses (sad) of rm-718 weekly (rm-718) in healthy subjects 18 to 55 years of age with obesity (part a), multiple ascending doses (mad) of rm-718 in healthy subjects 18 to 55 years of age with obesity (part b), and mad of rm-718 in patients 12 to 65 years of age with ho (part c). cohorts in parts a and b are double-blind, placebo-controlled, and randomized 2:1 (4 subjects receive rm-718, 2 subjects receive placebo). part c evaluates open-label dose escalation in patients 12 to 65 years of age with ho. study participants will receive: 1 weekly dose of either rm-718 or placebo in part a, 4 weekly doses of either rm-718 or placebo in part b, and 16 weekly doses of open-label rm-718 in part c. study drug (rm-718 or placebo) doses are administered weekly via subcutaneous injection.

Eligibility criteria:
key inclusion criteria: parts a and b: * male and female subjects in good health aged 18-55 years of age at screening. * body mass index (bmi) ≥30 kg/m2. * subjects who are medically healthy with normal or clinically insignificant screening results. * subjects must use a highly effective form of contraception and follow the study contraception requirements. * ability to communicate well with the investigator, understand and comply with the requirements of the trial, and understand english and sign the written informed consent. part c: * male and female patients with ho, aged 12-65 years of age at screening. * patient has documented evidence of acquired ho defined as: * diagnosis of craniopharyngioma or other brain lesion affecting the hypothalamic region and has undergone surgery, or chemotherapy, or radiation therapy involving the hypothalamus at least 6 months before screening, or * documented injury to the hypothalamus at least 6 months before screening for which surgery/radiation is not indicated. * weight gain associated with the hypothalamic injury either before or following therapy (surgery and/or following chemotherapy or radiotherapy), and a bmi of ≥30 kg/m2 for patients ≥18 years of age or bmi ≥95th percentile for age and sex for patients 12 to \<18 years of age. * patients must use a highly effective form of contraception and follow the study contraception requirements. * ability to communicate with the investigator, understand and comply with the requirements of the trial, and understand and sign the written informed consent and assent (for patients aged \<18 years), and informed consent for a parent or guardian of any patient \<18. key exclusion criteria: parts a and b * any clinically significant abnormalities on screening laboratories or physical examination as determined by the investigator. * active or history of any significant medical condition such as and including renal, hepatic, pulmonary, gastrointestinal, cardiovascular, genitourinary, endocrine, immunologic, metabolic, neurologic or hematological disease. * obesity due to genetic, syndromic, or endocrine etiologies. * history of renal transplant, end stage renal disease. * diagnosis of severe psychiatric disorders. * current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease considered severe enough to interfere with the trial and/or confound the results. * cigarette smoking or dependence on caffeine, alcohol or drugs; unable or unwilling to abstain completely from caffeine, alcohol and related substances for 24 hours prior to and after study visits. * history of recent surgery (within 60 days of screening). * participation in any clinical trial with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first trial dose. * pregnant and/or breastfeeding or desiring to become pregnant during this trial. part c * diagnosis of prader-willi syndrome (pws) or rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor syndrome (rohhadnet). * weight loss \>2% in the previous 3 months for patients aged ≥18 years or \>2% reduction in bmi for patients aged 12 to \<18 years and/or anti-obesity medications for the treatment of obesity. * bariatric surgery or procedure within the last 2 years. * diagnosis of severe psychiatric disorders; any suicidal ideation, attempt or behavior. * current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease considered severe enough to interfere with the trial and/or confound the results. * history of renal transplant, end stage renal disease. * participation in any clinical trial with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first trial dose, or previous participation in a trial with setmelanotide. * pregnant and/or breastfeeding or desiring to become pregnant during this trial. * obesity attributable to other genetic or syndromic conditions (eg, ppl \[pro-opiomelanocortin (pomc), proprotein convertase subtilisin/kexin type 1 (pcsk1), leptin receptor (lepr), collectively\], bardet-biedl syndrome \[bbs\]) prior to the hypothalamic injury. other protocol defined inclusion/exclusion criteria may apply.

Keywords: melanocortin 4 receptor (mc4r) mc4r agonism obesity